PROJECT SUMMARY Individuals ?65 years of age are the fastest growing demographic in the US. This population is significantly understudied, highly vulnerable to disease and accounts for at least $400 billion in Medicare costs per year. There is critical need for new biomarkers and risk factors that impact geriatric health to better serve this burgeoning population. The microbiome?the vast bacteria, fungi, and viruses inhabiting humans?has a ubiquitous role in immune homeostasis, metabolism, and pathogen exclusion, but its dysfunction has also been linked to numerous disorders. Given that it can harbor pathogens, virulence and antibiotic resistance genes, and pro-inflammatory stimuli, it is believed that it is an important contributor to geriatric disease. The goal of this proposal is to understand microbiome plasticity of skin, oral and gut microbiomes in older adults who have been living at a skilled nursing facility (SNF) and then transition back to the community because transitions between care settings predisposes older adults to skin, lung, urogenital, and gastrointestinal infections and varied co-morbidities. Two complementary studies are proposed using systems- genomics approaches and longitudinal cohorts in community-dwelling (CD) and SNF-dwelling (SNFD) older adults. These studies will characterize the skin, oral, and gut microbiome dynamics of SNFD and CD cohorts using deep shotgun metagenomic sequencing, which will reconstruct bacterial, fungal and viral strains, as well as functional elements to establish baseline characteristics, stability, and frequency of pathogenicity reservoirs. Aim 1 will establish the existence of population-level differences between microbiome profiles for individuals residing in different SNFs with relative stability of these measures over time. Aim 1 will characterize the microbial dynamics and pathogenicity reservoirs of CD and SNFD older adults, testing the hypothesis that the microbiota of older SNFD adults will exhibit 1) altered diversity, 2) increased pathogenicity reservoirs, and 3) greater instability over time, which are established metrics of reduced gut health. These characteristics will be investigated during the transition from SNFD to CD in Aim 2, with the hypothesis that as older adults transition from SNFs to the community, their microbiomes will increasingly assume features observed among CD older adults. The existence of individual-level microbial plasticity in response to environmental factors will then be established as clinically stable SNF residents transition back to the community. Understanding longitudinal dynamics will provide new insights into the role of the microbiome as a biomarker for transitional outcomes and is the necessary prerequisite for prospective studies investigating the role of the microbiome in adverse events during transition. This proposal?s multidisciplinary team has established SNF access, expertise in transition outcomes and geriatric care, clinical study design, and metagenomic sequencing and analyses. The finding this research will generate a new framework for understanding and investigating the geriatric microbiome and its predictive capacity in clinical outcomes.